Condom Use Doesn't Explain HIV and Depo-Provera Link

The use of depot medroxyprogesterone acetate (DMPA), branded as Depo-Provera, has been linked to an increased risk of HIV infection, according to an analysis of a dozen studies focused on women in sub-Saharan Africa.

The link is unexplained, and the authors emphasized that any discussion of the clinical implications must be balanced against the known benefits of DMPA as a highly effective contraceptive.

Key Points:

- DMPA has been linked to an increased risk of HIV infection in women in sub-Saharan Africa.

- Despite this link, DMPA remains an effective contraceptive.

- Whether DMPA should continue to be used in women at risk for HIV has become a subject of debate.

"We embarked on this study because of the inconsistency in the scientific literature on this topic," said lead study author Lauren Ralph, MPH, who conducted this research for her doctoral dissertation in epidemiology at the University of California, Berkeley, in a news release. "The results have potentially broad implications because hormonal contraceptives remain popular for women worldwide."

The analysis, which looked at data from a dozen studies, found that women who used DMPA had a 40% increased risk of acquiring HIV compared with women using nonhormonal contraception and those not practicing birth control.

This risk appeared to be lower among women in the general population, who saw an increased risk of 31%, than among women who were considered at high risk for acquiring HIV infection, the authors noted. However, there were a limited number of studies on high-risk women, leaving uncertainty in making the distinction between the general population and women already at high risk for the infection.

"The moderate elevation in risk for DMPA is not enough to justify a complete withdrawal of DMPA from women's contraceptive options in most settings," said lead study author Ralph in a press release. "This is likely to lead to more unintended pregnancies and their associated maternal and infant morbidity and mortality."

There was no evidence of an increased risk of HIV infection in ten studies of oral contraceptive pills or five studies of norethisterone enanthate, the research found. The authors suggested that it is possible that birth control with higher levels of progestin may alter the vaginal lining or have an impact on local immunity, increasing the risk for HIV infection. But the analysis did not include an examination of the physiological effects of the different contraceptive methods. To better understand any potential biologic mechanisms leading to the increased risk, more research is needed, the authors emphasized.

On hearing these results, the most obvious explanation for the increase in HIV infection is failure to use condoms. As such, the authors cited the potential "confounding effects of misreported condom use" as a limitation of the study, especially since "many study populations were drawn from HIV prevention trials in which condom use is strongly encouraged and women may feel pressure to report socially acceptable behaviors," they wrote. But they added that over-reporting of condom use was likely the same in all groups studied, including the reference samples. Therefore, condom use doesn't wholly explain the elevated risk in the DMPA study population.

The findings were published online in The Lancet Infectious Diseases this month.